Molecular analysis of familial androgen insensitivity syndrome due to replacement of glutamic acid 802 by lysine

We studied a Japanese family presenting at least two cases of complete andr ogen insensitivity syndrome (CAIS) and negative androgen receptor binding. The index subject showed a 46, XY karpotype and a complete female phenotype , For the purpose of further diagnosis and genetic counseling, molecular an alysis of the androgen receptor (AR) gene was performed. Direct sequencing of the AR gene identified a mutation at nucleotide 2935 (A --> G). This rep lacement was a novel missense mutation, resulting in the substitution of gl utamic acid 802 by lysine which deleted a recognition site for EcoRI in exo n 6 of the AR gene. We identified another affected individual, using chromo some and molecular analysis of the AR gene at exon 6. Furthermore, although heterozygote carriers could not be identified on clinical grounds, molecul ar identification of healthy individuals and heterozygote carriers in the f amily members provided definitive information for genetic counseling. We be lieve that the molecular analysis of familial CAIS is very informative for both the affected individuals and other family members.